Hypoglycemia is the most critical acute complication of diabetes. Typically used present methods of self-monitoring of blood glucose (SMBG) provide periodic measurements of blood glucose obtained from a finger stick. This method produces measurements that, while very accurate, are too infrequent to detect hypoglycemic episodes. Frequently, in order to avoid hypoglycemia, diabetics maintain abnormally high blood glucose levels to provide a “buffer” against low blood glucose levels. This constant high blood glucose level is the root cause of most long-term complications of diabetes, namely, retinopathy, neuropathy, nephropathy, and cardiovascular disease. In effect, the present SMBG methods are forcing many diabetics to pay for a lower rate of acute complications with a higher rate of chronic complications in later life.
The Diabetes Control and Complications Trial (DCCT) (The Diabetes Control and Complications Trial Research Group. New Engl. J. Med. 329, 977-1036 (1993)) clearly showed that more blood glucose information is essential to better clinical outcomes. The subject group that measured blood glucose and administered insulin more frequently (3-7 times per day) had a substantially lower rate of complications at the end of the study relative to the group that tested and injected less frequently. Even so, the tight control group was only able to reduce the average blood glucose to a value approximately 50% above normal (153 mg/dL). Similarly, the HbA1c levels (a measure of average blood glucose level over time) were lowered substantially relative to the control group, but not into the normal range. As a result of this more intensive therapy, the tight control group experienced hypoglycemic events three times more often than the control group. These results demonstrate that three to seven blood glucose measurements per day are sufficient to lower longer-term complication rates, but still do not provide enough information to bring average blood glucose levels to normal, or to prevent hypoglycemic events. Similar results have been obtained for subjects on oral medication (UK Prospective Diabetes Study (UKPDS) Group, Lancet 352:837-853 (1998); Ohkubo Y, et al., Diabetes Research & Clinical Practice 28:103-17 (1995)), demonstrating the general benefit of frequent glucose monitoring in the management of diabetes. However, Bolinder, et al., (Diabetes Care 20:64-70 (1997)) show that even seven measurements per day fail to detect more than one-third of all hypoglycemic events.